(1) Field of the Invention
The present invention relates to a method which uses anthocyanins, anthocyanidins or mixtures thereof to increase insulin production by cells. The present invention also relates to compositions to be used in the method for producing the increase in production of the insulin. The method and compositions can be in vivo or in vitro.
(2) Description of Related Art
The function of insulin is to maintain normal blood glucose levels either by suppression of glucose output from liver or by the stimulation of glucose uptake and its metabolism (Ross, S. A., et al., Chemistry and Biochemistry of diabetes. Chem. Rev. 104 1255-1282 (2004)). Insufficient release of insulin or loss of insulin action at target tissues causes aberrant glucose and lipid metabolism. This results in elevated glucose levels in the blood, a hallmark of diabetes (Jovanovic, L., et al. Type-2 diabetes: The epidemic of new millennium. Ann. Clin. Lab. Sci. 29 33-42 (1999)). There are two types of diabetes, type-1 (insulin-dependent diabetes) and type-2 diabetes (non-insulin-dependent diabetes). Type-1 diabetes results from autoimmune destruction of pancreatic β-cells, the cells that secrete insulin, which leads into insulin insufficiency. Type-2 diabetes is more prevalent and is caused by the inability of β-cells to secrete sufficient amounts of insulin to overcome insulin resistance established by genetic and environmental factors (Henquin, J. C., Diabetes 49 1751-1760 (2000)). The insulin resistance is a disorder in which insulin inadequately stimulates glucose transport in skeletal muscle and fat and inadequately suppresses hepatic glucose production. The mechanisms involved that prevent the β-cell from secreting sufficient amounts of insulin to overcome peripheral insulin resistance remain to be established. Oral hypoglycemic agents that directly stimulate insulin release from β-cells (e.g. sulfonylurea based drugs), however, have shown that insulin secretion from islets of type-2 diabetic patients can be elevated sufficiently to overcome peripheral insulin resistance and normalize blood glucose levels. One of the disadvantages of using sulfonylurea-based drugs is that it fails to control normal blood glucose levels (Pfeiffer, A. F. H., Oral hypoglycemic agents: Sulfonylureas and meglitinides. In B. J. Goldstein, et al., (Eds.), Test book of Type-2 Diabetes. Martin Dunitz Ltd., London pp. 77-85 (2003)). These drugs also adversely affect the ability of S-cells to secrete insulin and cause weight gain ((Pfeiffer, A. F. H., Oral hypoglycemic agents: Sulfonylureas and meglitinides. In B. J. Goldstein, et al., (Eds.), Test book of Type-2 Diabetes. Martin Dunitz Ltd., London pp. 77-85 (2003)). Hence, there is a role for dietary constituents that can regulate blood glucose level or induce insulin production by pancreatic β-cell.
The consumption of a diet low in fat and rich in antioxidants reduces the risk of obesity and insulin resistance (Blakely, S., et al., J. Nutr. 133 2838-2844 (2003)). Anthocyanins belong to antioxidant polyphenols and are present in various foods and beverages. Consumption of anthocyanins is associated with reduced risk of several degenerative diseases such as atheroscelerosis, cardiovascular disease, cancer and diabetes (Jayaprakasam, B., et al., Potent lipid peroxidation inhibitors from Withania somnifera. Tetrahedron 60 3109-3121 (2004)). These compounds are well-known free radical scavengers and reported as potential chemopreventive agents (Duthie, G. G., et al., Nutr. Res. Rev. 13 79-106 (2000)). For example, serum antioxidant capacity was increased by the consumption of strawberries, cherries, and red wine (Kang, S. Y., et al., Canc. Lett. 194 13-19 (2003); Van Velden, D. P., et al., Ann. New York Acad. Sci. 957 337-340 (2002); and Wang, H., et al., J. Nat. Prod. 62 294-296 (1999)). Recent studies demonstrated that the anthocyanin, cyanidin 3-glucoside, reduced the high fat diet induced obesity in mice (Tsuda, T., et al., J. Nut. 133 2125-2130 (2003)). Therefore, the natural colorants present in the food have attracted consumers due to their safety, nutritional and therapeutic values (Espin, J. C., et al., J. Agri. Food Chem. 48 1588-1592 (2000)). Since anthocyanins are widely consumed, additional biological activities of these compounds will be of great interest.
The fruits of the Cornus species are a rich source of anthocyanins. The fruits of Cornus mas L., also known as the European and Asiatic Cornelian cherry, are used in the preparation of beverages in Europe (Millspaugh, C. F., In American Medicinal Plants; Dover Publications: New York, 282 (1974)). In traditional medicine, Cornus officinalis fruits are known for their analgesic and diuretic activities (Kim, D. K., et al., Arch. Pharm. Res. 21 787-789 (1998)). The Cornus fruits are also one of the major constituents of several antidiabetic herbal preparations in Asian countries (Yamahara, J., et al., Yakugaku Zasshi 101 86-90 (1981)). Our earlier investigation of the fruits of C. mas and C. officinalis revealed that both contained high levels of anthocyanins (Seeram, N. P., et al., J. Agri. Food chem. 50 2519-2523 (2002)).